Studies of a variety of human colorectal adenocarcinomas will be conducted, using cells in culture and tumors grown as xenografts in immune-deprived mice, while measurements of the activities of enzymes concerned with the salvage of uracil, uridine and cytidine will be made, not only these tumors, but also in others, as well as in normal tissues. Determinations of the levels of these pyrimidine-containing compounds in blood and other tissues will be carried out. Immune-deprivation will be accomplished with a new murine anti-thymocyte serum (ATS), of goat-origin, injected into thymectomized mice, or in mice prepared by thymectomy, irradiation, and the injection of syngeneic bone marrow; these methods will continue to be compared in different strains of mice and with a variety of human xenografts, while the growth of both real and artificially produced metastases and their response to drugs will be examined. Investigations in culture, as well as in vivo, will be designed to elucidate the mechanisms of action of 5-fluorouracil (FU) and its metabolic derivatives, esecially 5-fluorouridine (FUR). The chemotherapeutic potential of FUR and FU, particularly as affected by massive doses of thymidine, will be studied. The synergistic effects of these and other drugs, especially of compounds now being synthesized, will be examined, mechanistically, both in culture and in mice with human xenografts of colorectal adenocarcinomas, with a view to potential improvements in mice with human xenografts of colorectal adenocarcinomas, with a view to potential improvements in the therapeutic control of this grave neoplastic disease of man.